Syntheses of a broad variety of novel derivatives of dihydrobiopterin (BH2), differing from the natural cofactor both in stereochemistry and in the nature of the C-6 side-chain, are proposed. Many of these compounds are designed as prodrugs of BH2 and should be capable of in vivo transformation into the natural cofactor. Synthetic routes are also proposed to all of the intermediates thus far suggested along the biosynthetic pathway from dihydroneopterin criphosphate to BH2. It is hoped that some of these derivatives of and biosynthetic intermediates to BH2 may be capable of passing the blood-brain barrier. These compounds should prove useful in the treatment of genetic disorders (Parkingson's disease, hyperphenylalaninemia) in which the metabolic errors leading to the disease symptoms are associated with a defect in BH2 biosynthesis. The availability of the biosynthetic intermediates to BH2 should also make it possible to identify the position of the biosynthetic defect. Some of these compounds may prove to be inhibitors of the monooxygenase enzymes (phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase) and thus be useful in the treatment of high-blood pressure, and in investigations of dopaminergic, noradrenergic and serotonergic neuronal pathways. There is heavy emphasis in this proposal on the development of new synthetic methods in heterocyclic chemistry.